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the IHC “1+” or “0” and FISH-positive group [ 11 ]. Others

have found some negative cases by immunohistochemistry

showed a low level of amplification and amplification by ratio

only without >6 copy number N [ 48 , 50 ]. A reliable immuno-

histochemical score of “1+” or “0” result confers HER2 status

to be negative and ISH confirmation is not required according

to experts [ 47 – 49 ]. Trastuzumab is a monoclonal antibody that

targets the protein product that could be tested by immunohis-

tochemistry. Hence, it can be argued that IHC result alone can

be the determinant of the HER2 status to confer eligibility for

anti-Her2 therapy. An IHC score of “3+” demonstrated by a

well-tested validated method performed by experts can be

regarded adequate for a positive result [ 45 , 49 ]. However, given

the host of issues discussed above, it is also safe to recommend

confirmation of high immunohistochemical score (IHC = “3+”)

cases by gene amplification before commencing anti-HER2

therapy. This is to avoid toxic and costly treatment to potential

ineligible patents especially if testing is performed in community

setting. A recent study has shown false-positive IHC results

with signet ring cell type adenocarcinomas [ 51 ]. All equivocal

immunohistochemical result (IHC score = “2+”) should be

tested with in situ hybridization. Internal and external audits of

testing at all levels and subscribing to quality assurance pro-

grams should be made mandatory with centralized testing

encouraged to ensure accurate results.

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